Esophageal cancer is a common malignancy with a very poor prognosis. The principal reason for its poor prognosis is that most tumors are asymptomatic and go undetected until they have spread beyond the esophageal wall and are unresectable. Significant reduction in esophageal cancer mortality will require successful strategies to diagnose and treat more cases at earlier, more curable stages of disease. A successful early detection program will require an accurate, patient-acceptable screening test, confirmatory tests that can localize precursor and early invasive lesions, and one or more curative therapies that are acceptable to asymptomatic patients. This project includes five studies designed to evaluate techniques that may be useful in such an early detection program: a. The Cytology Sampling Study will estimate and compare the sensitivity of several cytologic samplers for identifying biopsy-proven dysplasia and cancer of the esophagus. b. The Mucosal Staining Study will evaluate whether mucosal staining can improve endoscopic localization of esophageal dysplasia and cancer. c. The Endoscopic Staging Study will evaluate how accurately endoscopic techniques can stage dysplasia and early invasive cancer of the esophagus. d. The Endoscopic Therapy Pilot Study will evaluate the feasibility, safety, acceptability and preliminary efficacy of endoscopic therapies for removing or ablating focal high-grade dysplasias and early invasive cancers of the esophagus. The Chemoregression Study will evaluate the ability of oral chemopreventive agents to reduce progression or cause regression of low- grade squamous dysplasia of the esophagus. This project will be carried out in Linxian, China, a county with extraordinary rates of esophageal cancer and a correspondingly high prevalence of the asymptomatic precursor and early invasive lesions that are needed for these studies. The project will be a collaborative effort of investigators from NCI, the Cancer Institute of the Chinese Academy of Medical Sciences, and several U.S. universities.